How did the gut microbiome differ in people with untreated tuberculosis?

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The link between gut microbes and host immunity has prompted many studies of the gut microbiome in tuberculosis (TB), but those studies had not explored the community’s metabolic capacity, an important way it can affect immunity.

Researchers used deep sequencing of fecal samples from 23 treatment-naive TB patients and 48 healthy donors to reconstruct the gut microbiome’s metabolic capacity and its strain- and species-level composition. The abstract reports strong taxonomic divergence in the patients’ gut communities. Diverse disease-associated pathobionts together expanded to one-quarter of the total gut microbiota in patients, suggesting a heavy burden on host immunity alongside Mycobacterium tuberculosis (MTB) infection.

Metabolic pathway reconstruction indicated that the patients’ microbial communities had shifted toward rapid growth using glycolysis and excess fermentation to produce acetate and lactate. The authors propose that greater glucose availability in the intestine likely drives growth and fermentation to lactate, causing acidosis and endotoxemia.

The authors suggest that excessive fermentation and lactic acidosis likely characterize the disturbed gut microbiomes of TB patients. They note that lactic acidosis strongly suppresses normal gut flora, directly interferes with macrophage function, and is linked to mortality in TB patients. They highlight gut lactate acidosis as a new research focus; if confirmed, gut acidosis could be a potential host-directed treatment target to supplement traditional TB treatment.